We have defined further the alterations in membrane permeability and transport that occur after lectin treatment of normal blood lymphocytes and monocytes. First, we have defined mitogeninduced changes in human lymphocyte calcium metabolism. We have assessed the effect of the plant lectin phytohemagglutinin (PHA) on lymphocyte DNA synthesis, total cell calcium content and 45Ca labeling. Total cell calcium was not altered at optimal mitogenic PHA concentrations. However, at the minimum PHA concentrations that cause stimulation, the dose response of 45Ca uptake was very similar to that of DNA synthesis, and we could not stimulate DNA synthesis with PHA without increasing lymphocyte 45Ca labeling. These data suggest that an increase in total cell calcium is not essential for mitogenesis; however, an increase in 45Ca exchange is closely associated with the mitogenic effects of PHA. Second, we extended our studies of calcium transport to human monocyte plasma membrane vesicles. The data indicate that monocyte vesicles contain a highly specific, ATP-dependent calcium transport system, the energy for which is transduced by a calciumATPase with a high calcium affinity, which is virtually identical to that of the transport system. We have studied further the effect of concanavalin A (Con A) on monocyte calcium pools, using a non-linear least-squares analysis of 45Ca influx and efflux. Monocyte calcium was located in three exchangeable pools with influx time constants of 0.733, 0.048, and 0.012 min-1. The addition of a concentration of Con A that optimally stimulated superoxide production significantly increased the efflux time constant of pool no. 2 from 0.048 to 0.077 min-1, and the addition of alpha-methylmannoside prevented this increase. Thus, lectin stimulation of monocyte metabolism resulted in acceleration of calcium turnover in one of the cell calcium pools which likely represents the cytoplasmic component of monocyte calcium. Preliminary studies of cytoplasmic free calcium with fluorescing calcium ligands support this supposition.